Determination of genetic effects and functional SNPs of bovine HTR1B gene on milk fatty acid traits.
Dairy cattle
Genetic effects
HTR1B
Luciferase assay
Milk fatty acids
Journal
BMC genomics
ISSN: 1471-2164
Titre abrégé: BMC Genomics
Pays: England
ID NLM: 100965258
Informations de publication
Date de publication:
27 Jul 2021
27 Jul 2021
Historique:
received:
24
06
2021
accepted:
15
07
2021
entrez:
28
7
2021
pubmed:
29
7
2021
medline:
30
7
2021
Statut:
epublish
Résumé
Our previous genome-wide association study (GWAS) on milk fatty acid traits in Chinese Holstein cows revealed, the SNP, BTB-01556197, was significantly associated with C10:0 at genome-wide level (P = 0.0239). It was located in the down-stream of 5-hydroxytryptamine receptor 1B (HTR1B) gene that has been shown to play an important role in the regulation of fatty acid oxidation. Hence, we considered it as a promising candidate gene for milk fatty acids in dairy cattle. In this study, we aimed to investigate whether the HTR1B gene had significant genetic effects on milk fatty acid traits. We re-sequenced the entire coding region and 3000 bp of 5' and 3' flanking regions of HTR1B gene. A total of 13 SNPs was identified, containing one in 5' flanking region, two in 5' untranslated region (UTR), two in exon 1, five in 3' UTR, and three in 3' flanking region. By performing genotype-phenotype association analysis with SAS9.2 software, we observed that 13 SNPs were significantly associated with medium-chain saturated fatty acids such as C6:0, C8:0 and C10:0 (P < 0.0001 ~ 0.042). With Haploview 4.1 software, linkage disequilibrium (LD) analysis was performed. Two haplotype blocks formed by two and ten SNPs were observed. Haplotype-based association analysis indicated that both haplotype blocks were strongly associated with C6:0, C8:0 and C10:0 as well (P < 0.0001 ~ 0.0071). With regards to the missense mutation in exon 1 (g.17303383G > T) that reduced amino acid change from alanine to serine, we predicted that it altered the secondary structure of HTR1B protein with SOPMA. In addition, we predicted that three SNPs in promoter region, g.17307103A > T, g.17305206 T > G and g.17303761C > T, altered the binding sites of transcription factors (TFs) HMX2, PAX2, FOXP1ES, MIZ1, CUX2, DREAM, and PPAR-RXR by Genomatix. Of them, luciferase assay experiment further confirmed that the allele T of g.17307103A > T significantly increased the transcriptional activity of HTR1B gene than allele A (P = 0.0007). In conclusion, our findings provided first evidence that the HTR1B gene had significant genetic effects on milk fatty acids in dairy cattle.
Sections du résumé
BACKGROUND
BACKGROUND
Our previous genome-wide association study (GWAS) on milk fatty acid traits in Chinese Holstein cows revealed, the SNP, BTB-01556197, was significantly associated with C10:0 at genome-wide level (P = 0.0239). It was located in the down-stream of 5-hydroxytryptamine receptor 1B (HTR1B) gene that has been shown to play an important role in the regulation of fatty acid oxidation. Hence, we considered it as a promising candidate gene for milk fatty acids in dairy cattle. In this study, we aimed to investigate whether the HTR1B gene had significant genetic effects on milk fatty acid traits.
RESULTS
RESULTS
We re-sequenced the entire coding region and 3000 bp of 5' and 3' flanking regions of HTR1B gene. A total of 13 SNPs was identified, containing one in 5' flanking region, two in 5' untranslated region (UTR), two in exon 1, five in 3' UTR, and three in 3' flanking region. By performing genotype-phenotype association analysis with SAS9.2 software, we observed that 13 SNPs were significantly associated with medium-chain saturated fatty acids such as C6:0, C8:0 and C10:0 (P < 0.0001 ~ 0.042). With Haploview 4.1 software, linkage disequilibrium (LD) analysis was performed. Two haplotype blocks formed by two and ten SNPs were observed. Haplotype-based association analysis indicated that both haplotype blocks were strongly associated with C6:0, C8:0 and C10:0 as well (P < 0.0001 ~ 0.0071). With regards to the missense mutation in exon 1 (g.17303383G > T) that reduced amino acid change from alanine to serine, we predicted that it altered the secondary structure of HTR1B protein with SOPMA. In addition, we predicted that three SNPs in promoter region, g.17307103A > T, g.17305206 T > G and g.17303761C > T, altered the binding sites of transcription factors (TFs) HMX2, PAX2, FOXP1ES, MIZ1, CUX2, DREAM, and PPAR-RXR by Genomatix. Of them, luciferase assay experiment further confirmed that the allele T of g.17307103A > T significantly increased the transcriptional activity of HTR1B gene than allele A (P = 0.0007).
CONCLUSIONS
CONCLUSIONS
In conclusion, our findings provided first evidence that the HTR1B gene had significant genetic effects on milk fatty acids in dairy cattle.
Identifiants
pubmed: 34315401
doi: 10.1186/s12864-021-07893-8
pii: 10.1186/s12864-021-07893-8
pmc: PMC8314477
doi:
Substances chimiques
Fatty Acids
0
Serotonin
333DO1RDJY
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
575Subventions
Organisme : Beijing Science and Technology Program
ID : 20200105, D171100002417001
Organisme : National Science and Technology Programs of China
ID : 2013AA102504
Organisme : National Natural Science Foundation of China
ID : 31872330, 31802041
Organisme : Earmarked Fund for Modern Agro-industry Technology Research System
ID : CARS-36
Organisme : the Program for Changjiang Scholar and Innovation Research Team in University
ID : IRT_15R62
Informations de copyright
© 2021. The Author(s).
Références
J Nutr. 2018 Dec 1;148(12):1938-1945
pubmed: 30517725
Cell Physiol Biochem. 2018;51(3):1301-1312
pubmed: 30481776
ACS Chem Biol. 2017 Mar 17;12(3):724-734
pubmed: 28094913
Protein Sci. 1996 May;5(5):947-55
pubmed: 8732766
Cancer Cell Int. 2018 Mar 20;18:40
pubmed: 29568235
J Dairy Sci. 2009 Sep;92(9):4664-75
pubmed: 19700730
J Dairy Sci. 2003 Aug;86(8):2588-97
pubmed: 12939083
J Dairy Sci. 2017 Jun;100(6):4731-4744
pubmed: 28342614
BMC Mol Cell Biol. 2020 Nov 24;21(1):83
pubmed: 33228519
PLoS One. 2014 May 23;9(5):e96186
pubmed: 24858810
Sci Adv. 2019 Dec 11;5(12):eaax8898
pubmed: 31844668
Genome Res. 2020 May;30(5):790-801
pubmed: 32424068
J Anim Breed Genet. 2016 Oct;133(5):384-95
pubmed: 26968150
Cell. 2009 Mar 6;136(5):903-12
pubmed: 19269367
Chin Med J (Engl). 2017 Aug 5;130(15):1779-1784
pubmed: 28748849
Curr Atheroscler Rep. 2018 Mar 21;20(5):24
pubmed: 29564646
Development. 2005 Sep;132(18):4119-30
pubmed: 16107479
DNA Cell Biol. 2021 Feb;40(2):219-230
pubmed: 33332227
Am J Clin Nutr. 1999 Dec;70(6):1009-15
pubmed: 10584045
Dev Biol. 2010 Mar 15;339(2):507-18
pubmed: 20043901
J Mol Biol. 1997 Jul 18;270(3):471-80
pubmed: 9237912
Genetics. 1996 Dec;144(4):1799-808
pubmed: 8978065
Curr Top Med Chem. 2015;15(14):1323-58
pubmed: 25866275
Clin Cancer Res. 2017 Aug 15;23(16):4693-4703
pubmed: 28446506
Dev Genes Evol. 2001 Jul;211(7):338-49
pubmed: 11466530
Mamm Genome. 1995 Jun;6(6):383-8
pubmed: 7647458
Foods. 2018 Mar 01;7(3):
pubmed: 29494487
Dev Biol. 1997 Nov 15;191(2):215-29
pubmed: 9398436
Mol Cell. 2014 Jul 3;55(1):5-14
pubmed: 24996062
J Dairy Sci. 2009 Sep;92(9):4676-82
pubmed: 19700731
PLoS One. 2012;7(10):e46688
pubmed: 23056405
Development. 2002 May;129(9):2099-108
pubmed: 11959820
Sci Rep. 2015 Feb 16;5:8465
pubmed: 25682954
J Biomol Struct Dyn. 2004 Apr;21(5):625-38
pubmed: 14769055
Biochem J. 1952 May;51(2):251-8
pubmed: 14944582
Biomed Pharmacother. 2018 Oct;106:733-737
pubmed: 29990865
Sci Rep. 2018 Oct 29;8(1):15912
pubmed: 30374023
Annu Rev Genet. 2012;46:43-68
pubmed: 22934649
BMC Genet. 2013 Sep 11;14:79
pubmed: 24024882
Exp Cell Res. 2005 Jun 10;306(2):373-9
pubmed: 15925593
Carcinogenesis. 2011 Nov;32(11):1713-23
pubmed: 21880579
Nat Protoc. 2009;4(7):1073-81
pubmed: 19561590
J Mol Cell Biol. 2019 Apr 1;11(4):267-276
pubmed: 30496442